Investigation of single-cell and population dynamics of hippocampal networks
OA Version
Citation
Abstract
The hippocampus is crucial for various cognitive tasks, including learning and memory. This dissertation investigates the dynamics of hippocampal CA1 neural networks across cellular and network scales during behavior and pathology, using cutting-edge, large scale cellular calcium and voltage imaging from many individual neurons simultaneously in behaving mice. First, we quantified cellular calcium changes in a mouse model of autism spectrum disorder (ASD) that has a complete knockout (KO) of the ASD-causative gene, NEXMIF. We discovered NEXMIF KO increased the locomoting encoding ability of individual CA1 neurons, but it caused network over-synchronization across individual neurons, which could reduce network information encoding capability and contribute to the behavioral disruptions previously reported in NEXMIF KO. Next, we employed large-scale voltage imaging to understand how subthreshold dynamics versus suprathreshold spiking code spatial information during navigation. We found that in many neurons, subthreshold membrane voltage (Vm) exhibits prominent theta (6-10Hz) fluctuations, and the relative phases of Vm theta between simultaneously recorded neurons encode spatial information. This finding provides a new framework of network information processing through phase shifts in subthreshold dynamics which are dominated by synaptic inputs, independent of spiking. Through large and medium scale optical imaging of neurons, our findings reveal how single-neuron dynamics are integrated within larger neural networks, and advance our understanding of the hippocampal coding of behavior and pathology.
Description
2026
License
Attribution-NonCommercial-NoDerivatives 4.0 International